Programmed cell death or apoptosis is the process through which multicellular animals eliminate unwanted and potentially dangerous cells from their body. Deregulating programmed cell death in humans can lead to disease, such as various types of cancer, autoimmune diseases and neurodegenerative diseases demonstrating the importance of this process for human health. Studies performed over the last decade have resulted in the identification of the major components of the central, conserved machinery required to bring about programmed cell death. However, little is known thus far about how this central machinery is regulated. The long-term goal of our investigation is to determine how programmed cell death is controlled in the nematode Caenorhabditis elegans, genetic studies of which have been pioneering in the elucidation of the central cell death machinery. Our studies focus on the analysis of the programmed death of germ cells in the gonad of adult C. elegans hermaphrodites and the programmed death of two types of somatic cells, the NSM sister cells and the CEMs, during development. In order to identify factors involved in the regulation of these three cell death events, we have developed tools for their efficient detection. These tools we have used to identify C. elegans mutants defective specifically in germ cell death, the NSM sister cell death or the CEM death. The molecular characterization of the affected genes will provide insight into the nature of the mechanisms involved in activating the central cell death machinery in specific tissues or specific cells. Furthermore, we will analyze the function of the affected proteins and determine how they control the activity of the central cell death machinery. Since the pathways involved in regulating programmed cell death also seem to be conserved, results from these studies will improve our current understanding of cell death regulation not only in C. elegans but in higher organisms, including humans, as well.